ABSTRACT

This study was to investigate the effects of oxidative stress in cigarette smoke (CS)-induced cell apoptosis in mice with emphysema. Thirty-two mice were divided into four groups: the control group, the CS group, the CS + Pifithrin-α group, and the CS + NAC group. Pathological changes and apoptosis in lung tissue of mice were detected. The activity of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) were measured using spectrophotometer. The proteins expression of p53, Bcl-2, Bax, and caspase-3 were determined by western blot. The results showed that cell apoptosis, lung structural damage, and the activity of MDA, as well as the expression of apoptosis-related proteins Bax, total caspase-3, and cleaved caspase-3 were increased in CS-treated mice. The activity of SOD, CAT, and T-AOC, as well as the expression of anti-apoptosis protein Bcl-2 were decreased in CS-treated mice when compared with the control group. However, Pifithrin-α (p53 inhibitor) and N-Acetylcysteine (NAC) could reduce cell apoptosis, lung structural damage and oxidative stress, accelerate the expression of Bcl-2, while suppressing the expression of Bax, total caspase-3 and cleaved caspase-3. More importantly, the treatment with NAC even inhibited the expression of p53. In conclusions, oxidative stress linking the p53 is involved in cell apoptosis in CS-treated emphysema mice.

 抽象的

本研究旨在探讨氧化应激对香烟烟雾（CS）诱导的肺气肿小鼠细胞凋亡的影响。 32只小鼠分为四组：对照组、CS组、CS+Pifithrin-α组和CS+NAC组。检测小鼠肺组织病理变化及细胞凋亡情况。使用分光光度计测定丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和总抗氧化能力（T-AOC）的活性。通过蛋白质印迹法测定p53、Bcl-2、Bax和caspase-3的蛋白表达。结果显示，CS处理的小鼠细胞凋亡、肺结构损伤、MDA活性以及凋亡相关蛋白Bax、总caspase-3和cleaved caspase-3的表达增加。与对照组相比，CS治疗组小鼠的SOD、CAT和T-AOC活性以及抗凋亡蛋白Bcl-2的表达均降低。然而，Pifithrin-α（p53抑制剂）和N-乙酰半胱氨酸（NAC）可以减少细胞凋亡、肺结构损伤和氧化应激，加速Bcl-2的表达，同时抑制Bax、总caspase-3和cleaved caspase的表达-3。更重要的是，NAC处理甚至抑制了p53的表达。总之，连接 p53 的氧化应激参与 CS 治疗的肺气肿小鼠的细胞凋亡。